Towards miniaturized closed-loop optogenetic stimulation devices

Objective. Electrical brain stimulation provides therapeutic benefits for patients with drug-resistant neurological disorders. It, however, has restricted access to cell-type selectivity which limits its treatment effectiveness. Optogenetics, in contrast, enables precise targeting of a specific cell type which can address the issue with electrical brain stimulation. It, nonetheless, disregards real-time brain responses in delivering optimized stimulation to target cells. Closed-loop optogenetics, on the other hand, senses the difference between normal and abnormal states of the brain, and modulates stimulation parameters to achieve the desired stimulation outcome. Current review articles on closed-loop optogenetics have focused on its theoretical aspects and potential benefits. A review of the recent progress in miniaturized closed-loop optogenetic stimulation devices is thus needed. Approach. This paper presents a comprehensive study on the existing miniaturized closed-loop optogenetic stimulation devices and their internal components. Main results. Hardware components of closed-loop optogenetic stimulation devices including electrode, light-guiding mechanism, optical source, neural recorder, and optical stimulator are discussed. Next, software modules of closed-loop optogenetic stimulation devices including feature extraction, classification, control, and stimulation parameter modulation are described. Then, the existing devices are categorized into open-loop and closed-loop groups, and the combined operation of their neural recorder, optical stimulator, and control approach is discussed. Finally, the challenges in the design and implementation of closed-loop optogenetic stimulation devices are presented, suggestions on how to tackle these challenges are given, and future directions for closed-loop optogenetics are stated. Significance. A generic architecture for closed-loop optogenetic stimulation devices involving both hardware and software perspectives is devised. A comprehensive investigation into the most current miniaturized and tetherless closed-loop optogenetic stimulation devices is given. A detailed comparison of the closed-loop optogenetic stimulation devices is presented.